Kawasaki Disease
Conditions
Keywords
Kawasaki disease, prednisolone, coronary artery lesion
Brief summary
This study evaluates the efficacy of the addition of prednisolone to conventional initial treatment (intravenous immunoglobulin \[IVIG\] plus aspirin) in reducing coronary artery lesion in children with Kawasaki disease (KD) .
Detailed description
This is a multicenter, open-label, blind-endpoints, randomized controlled trial at more than 10 hospitals in China. The investigators enrolled KD children diagnosed within 10 days of onset. Participants will be randomly assigned in a 1:1 ratio to the control group (receiving 2g/kg IVIG and 30 mg/kg aspirin) or the intervention group (receiving 2 g/kg IVIG, 30 mg/kg aspirin and additional 2 mg/kg prednisolone). Baseline characteristics of each participant will be collected, including sex, age of onset, height, body weight, subtype of KD, fever days before initial IVIG, echocardiographic findings at enrolment, and a series of pre-IVIG laboratory tests. Two-dimensional echocardiography will be performed at admission, 2 weeks, 1 month, 3 months, 6 months，and 12 months after onset of KD to assess the coronary artery lesions.
Interventions
DRUGIVIG
IVIG at a single dose of 2 g/kg, with the maximum dose of 60g
DRUGAspirin
Aspirin 30 mg/kg in oral per day (given in 3 divided doses), then 3 to 5 mg/kg per day when fever subsides for 3 days and C-reactive protein (CRP) is normal. Aspirin will be continued for at least 6 weeks after onset of illness.
DRUGPrednisolone
Intravenous methylprednisolone 1.6 mg/kg per day (given in 2 divided doses, with the maximum dose 60mg of prednisolone ) for 3 days, which is administered concurrently with the initial IVIG infusion and completed within 30-60 minutes, then changed to oral prednisolone 2 mg/kg when fever subsides for 3 days. If CRP is normal, the oral dose will be reduced every 5 days from 2 mg/kg to 1 mg/kg to 0.5 mg/kg (tapered over 15 days). Then prednisolone will be discontinued.
Sponsors
Children's Hospital of Fudan University
Jiangxi Province Children's Hospital
First People's Hospital of Hangzhou
Shengjing Hospital
The First Hospital of Jilin University
Chengdu Women's and Children's Central Hospital
Children's Hospital of Chongqing Medical University
Inner Mongolia People's Hospital
Sichuan Provincial People's Hospital
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Third Affiliated Hospital of Zhengzhou University
Children's Hospital of Soochow University
Yuying Children's Hospital of Wenzhou Medical University
Beijing Children's Hospital
Qilu Hospital of Shandong University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Participants and physicians will not be masked to the assignment. Pediatric cardiologists who assess coronary artery lesions (CAL) by echocardiography will be masked to the allocation.
Eligibility
Sex/Gender
ALL
Age
1 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Meeting diagnostic criteria for Kawasaki disease (KD) released by American Heart Association (AHA) in 2017 * Diagnosed before the tenth day of illness (with the first day of illness defined as the first day of fever) * Not treated with IVIG yet * Age ≥1 month
Exclusion criteria
* Z score of any coronary artery before initial treatment ≥10 * Receiving steroids or other immunosuppressive agents in the previous 30 days * With a previous history of KD * Afebrile before enrolment * With suspected infectious diseases including sepsis, septic meningitis, peritonitis, bacterial pneumonia, varicella and influenza * With serious immune diseases such as immunodeficiency or chromosomal abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of coronary artery lesions(CAL) at one month of illness | at one month of illness | Two-dimensional echocardiography will be performed to evaluate CAL at 1 month of illness. The measurement of each patient included the diameter of the left main coronary artery (LMCA), the left anterior descending artery (LAD), the left circumflex coronary artery (LCX), and the proximal and middle segments of the right coronary artery (RCA). Z score of each coronary artery will be calculated（Journal of the American Society of Echocardiography, 2011, 24(1).）. CAL is defined as z≥2of any coronary artery of LMCA, LAD, LCX, and the proximal and middle segment of the RCA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of the need for additional treatment | from admission to discharge (about 2 weeks of illness) | Axillary temperature (or rectal temperature) will be measured every 6 hours a day during hospitalization. Participants who have recurrent or persistent fever (axillary temperature ≥37.5°C or rectal temperature ≥38°C) after 36 hours of completion of initial IVIG infusion will be given additional treatment. |
| Duration of fever (hours) after initiation of initial IVIG infusion | from initiation of initial IVIG infusion to the first record of being afebrile(defined as an axillary temperature <37.5 for more than 24 hours) | Axillary temperature (or rectal temperature) will be measured every 6 hours a day during hospitalization. Participants with an axillary temperature \<37.5℃ (or rectal temperature \<38℃) for more than 24 hours are considered afebrile. Record the time of the initiation of IVIG infusion and the time of the body temperature first becoming normal. |
| Changes in z scores of LMCA throughout the study period | from admission to 12 months of illness | This is a repeated measurement. The internal diameter of LMCA will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）. |
| Changes in z scores of LAD throughout the study period | from admission to 12 months of illness | This is a repeated measurement. The internal diameter of LAD will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）. |
| Changes in z scores of LCX throughout the study period | from admission to 12 months of illness | This is a repeated measurement. The internal diameter of LCX will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）. |
| Changes in z scores of the proximal segment of RCA throughout the study period | from admission to 12 months of illness | This is a repeated measurement. The internal diameter of the proximal segment of RCA will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）. |
| Changes in z scores of the middle segment of RCA throughout the study period | from admission to 12 months of illness | This is a repeated measurement. The internal diameter of the middle segment of RCA will be measured by echocardiography at six time points: at enrolment, at 2 weeks, 1 month, 3 months, 6 months and 12 months of illness. Z score will be calculated based on the height, weight and coronary artery diameter（Journal of the American Society of Echocardiography, 2011, 24(1).）. |
| Change in serum C-reactive protein (CRP) concentration | from admission to 72 hours after completion of initial IVIG infusion | CRP level is measured before initial IVIG infusion and 72 hours after completion of initial IVIG infusion. |
| Number of patients with serious adverse events | from admission to 3 months of illness | This is a composite outcome, including death, hypertension, severe infection, allergic reactions, heart failure, thrombosis, etc. |
| Occurrence of medium-to-giant coronary artery aneurysms (CAAs) | from admission to 12 months of illness onset | Exploratory Outcome. This is a repeatedly measured binary variable. CAL classification is based on the maximum z score according to the 2017 American Heart Association guideline. Medium CAA is defined as a maximum Z score ≥5 to \<10, and all internal diameters \<8 mm; large or giant CAA is defined as a maximum Z score ≥10, or any internal diameter ≥8 mm. Data were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively. |
| Occurrence of large/giant CAAs | from admission to 12 months of illness onset | Exploratory Outcome. This is a repeatedly measured binary variable. CAL classification is based on the maximum z score according to the 2017 American Heart Association guideline. Medium CAA is defined as a maximum Z score ≥5 to \<10, and all internal diameters \<8 mm; large or giant CAA is defined as a maximum Z score ≥10, or any internal diameter ≥8 mm. Data were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively. |
| Occurrence of CAL progression within 3 months of illness onset | from admission to 3 months of illness onset | Exploratory outcome. CAL progression is defined as an increment in the Z score ≥1 from admission in any coronary artery (LMCA, LAD, LCX, proximal and middle segments of RCA) at any given time point within 3 months of illness onset. The outcome was assessed in all participants and those with CAL at baseline. |
| Changes in absolute diameter of LMCA throughout the study period | from admission to 12 months of illness onset | Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of LMCA were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively. |
| Changes in absolute diameter of LAD throughout the study period | from admission to 12 months of illness onset | Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of LAD were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively. |
| Changes in absolute diameter of LCX throughout the study period | from admission to 12 months of illness onset | Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of LCX were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively. |
| Changes in absolute diameter of the proximal segment of RCA throughout the study period | from admission to 12 months of illness onset | Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of the proximal segment of RCA were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively. |
| Changes in absolute diameter of the middle segment of RCA throughout the study period | from admission to 12 months of illness onset | Exploratory outcome. This is a repeatedly measured continuous variable. The absolute internal diameter of the middle segment of RCA were and will be collected at six time points of illness: enrollment, 2th week (±2 days), 1th month (+5 days), 3th month (±5 days), 6th month (±5 days) and 12th month (±5 days), respectively. |
Countries
China
Contacts
STUDY_DIRECTORFang Liu, MD.
Children's Hospital of Fudan University
Outcome results
None listed